Abstract:
:Filamentous cyanobacteria belong to the most prolific producers of structurally unique and biologically active natural products, yet the majority of biosynthetic gene clusters predicted for these multicellular collectives are currently orphan. Here, we present a systems analysis of secondary metabolite gene expression in the model strain Nostoc punctiforme PCC73102 using RNA-seq and fluorescence reporter analysis. Our data demonstrate that the majority of the cryptic gene clusters are not silent but are expressed with regular or sporadic pattern. Cultivation of N. punctiforme using high-density fermentation overrules the spatial control and leads to a pronounced upregulation of more than 50% of biosynthetic gene clusters. Our data suggest that a combination of autocrine factors, a high CO2 level, and high light account for the upregulation of individual pathways. Our overarching study not only sheds light on the strategies of filamentous cyanobacteria to share the enormous metabolic burden connected with the production of specialized molecules but provides an avenue for the genome-based discovery of natural products in multicellular cyanobacteria as exemplified by the discovery of highly unusual variants of the tricyclic peptide microviridin.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Dehm D,Krumbholz J,Baunach M,Wiebach V,Hinrichs K,Guljamow A,Tabuchi T,Jenke-Kodama H,Süssmuth RD,Dittmann Edoi
10.1021/acschembio.9b00240subject
Has Abstractpub_date
2019-06-21 00:00:00pages
1271-1279issue
6eissn
1554-8929issn
1554-8937journal_volume
14pub_type
杂志文章abstract::The innate immune system provides the first line of defense against pathogens through the recognition of nonspecific patterns in RNA to protect the cell in a generalized way. The human RNA-activated protein kinase, PKR, is a dsRNA binding protein and an essential sensor in the innate immune response, which recognizes ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.6b00081
更新日期:2016-04-15 00:00:00
abstract::Polyhalogenated dibenzo-p-dioxins are arguably among the most toxic molecules known to man. In addition to anthropogenic sources, marine invertebrates also harbor polybrominated dibenzo-p-dioxins of as yet unknown biogenic origin. Here, we report that the bmp gene locus in marine bacteria, a recently characterized sou...
journal_title:ACS chemical biology
pub_type: 信件
doi:10.1021/cb5004338
更新日期:2014-09-19 00:00:00
abstract::The Akt kinase family, consisting of three isoforms in humans, is a well-validated class of drug target. Through various screening campaigns in academics and pharmaceutical industries, several promising inhibitors have been developed to date. However, due to the mechanistic and structural similarities of Akt kinases, ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb200388k
更新日期:2012-03-16 00:00:00
abstract::Binding of the Fc domain of Immunoglobulin G (IgG) to Fcγ receptors on leukocytes can initiate a series of signaling events resulting in antibody-dependent cell-mediated cytotoxicity (ADCC) and other important immune responses. Fc domains lacking glycosylation at N297 have greatly diminished Fcγ receptor binding and l...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb300130k
更新日期:2012-09-21 00:00:00
abstract::Post-translational modifications of histones alter chromatin structure and play key roles in gene expression and specification of cell states. Small molecules that target chromatin-modifying enzymes selectively are useful as probes and have promise as therapeutics, although very few are currently available. G9a (also ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb300139y
更新日期:2012-07-20 00:00:00
abstract::Terpene synthases (TS) are classified into two broad types, Class I and II, based on the chemical strategy for initial carbocation formation and motif sequences of the catalytic site. We have recently identified a new class of enzymes, Class IB, showing the acceptability of long (C20-C35) prenyl-diphosphates as substr...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00145
更新日期:2020-06-19 00:00:00
abstract::The gibberellin (GA) phytohormones are produced not only by plants but also by fungi and bacteria. Previous characterization of a cytochrome P450 (CYP)-rich GA biosynthetic operon found in many symbiotic, nitrogen-fixing rhizobia led to the elucidation of bacterial GA biosynthesis and implicated GA9 as the final produ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.6b01038
更新日期:2017-04-21 00:00:00
abstract::Miniproteins have a size between that of larger biologics and small molecules and presumably possess the advantages of both; they represent an expanding class of promising scaffolds for the design of affinity reagents, enzymes, and therapeutics. Conventional strategies to promote cellular uptake of miniproteins rely o...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.8b00564
更新日期:2018-11-16 00:00:00
abstract::Protein dimerization provides a mechanism for the modulation of cellular signaling events. In α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors, the rapidly desensitizing, activated state has been correlated with a weakly dimeric, glutamate-binding domain conformation. Allosteric modulators can fo...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb4007166
更新日期:2014-01-17 00:00:00
abstract::Methods for the rapid identification of defined cell growth conditions are lacking. This deficiency is a major barrier to the investigation and application of human embryonic stem (ES) cells. To address this problem, we developed a method for generating arrays of self-assembled monolayers (SAMs) in which each element ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb700032u
更新日期:2007-05-22 00:00:00
abstract::Angiogenesis, the formation of new blood vessels, is implicated in a number of important human diseases, including cancer, diabetic retinopathy, and rheumatoid arthritis. To identify clinically useful angiogenesis inhibitors, we assembled and screened a library of mostly Food and Drug Administration-approved drugs for...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb600362d
更新日期:2007-04-24 00:00:00
abstract::FAT10 is a ubiquitin-like protein suggested to target proteins for proteasomal degradation. It is highly upregulated upon pro-inflammatory cytokines, namely, TNFα, IFNγ, and IL6, and was found to be highly expressed in various epithelial cancers. Evidence suggests that FAT10 is involved in cancer development and may h...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00667
更新日期:2019-12-20 00:00:00
abstract::The publication of the first high-resolution crystal structure of a eukaryotic Cys-loop receptor, GluClα, has provided valuable structural information on this important class of ligand-gated ion channels (LGIC). However, limited functional data exist for the GluCl receptors. Before applying the structural insights fro...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb500323d
更新日期:2014-10-17 00:00:00
abstract::Streptolysin S (SLS) is a post-translationally modified peptide cytolysin that is produced by the human pathogen Streptococcus pyogenes. SLS belongs to a large family of azole-containing natural products that are biosynthesized via an evolutionarily conserved pathway. SLS is an important virulence factor during S. pyo...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb500843r
更新日期:2015-05-15 00:00:00
abstract::C-methylation of aromatic small molecules by C-methyltransferases (C-MTs) is an important biological transformation that involves C-C bond formation using S-adenosyl-l-methionine (SAM) as the methyl donor. Here, two advances in the mechanistic understanding of C-methylation of the 8-position of coumarin substrates cat...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.6b01053
更新日期:2017-02-17 00:00:00
abstract::Chemical cross-linking is well-established for investigating protein-protein interactions. Traditionally, photo cross-linking is used but is associated with problems of selectivity and UV toxicity in a biological context. We here describe, with live cells and under normal growth conditions, selective cross-linking of ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.7b00396
更新日期:2017-08-18 00:00:00
abstract::Thermodynamics and kinetics of protein-ligand binding are both important aspects for the design of novel drug molecules. Presently, thermodynamic data are collected with isothermal titration calorimetry, while kinetic data are mostly derived from surface plasmon resonance. The new method of kinITC provides both thermo...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00895
更新日期:2020-03-20 00:00:00
abstract::Understanding the complex biochemical mechanisms that underlie the regulation, toxicity, and protein binding of metal ions requires the ability to analyze the metal content of individual proteins in complex mixtures. In this issue of ACS Chemical Biology, a technique combining gel electrophoresis with synchrotron X-ra...
journal_title:ACS chemical biology
pub_type: 评论,杂志文章
doi:10.1021/cb100145z
更新日期:2010-06-18 00:00:00
abstract::Autophagy is a bulk, nonspecific protein degradation pathway that is involved in the pathogenesis of cancer and neurodegenerative disease. Here, we observed that xanthohumol (XN), a prenylated chalcone present in hops (Humulus lupulus L.) and beer, modulates autophagy. By using XN-immobilized beads, valosin-containing...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb200492h
更新日期:2012-05-18 00:00:00
abstract::Pathogenic Yersinia spp. secrete the effector YopJ (YopP) into host cells to counteract cytokine production and to induce programmed cell death (apoptosis). YopJ achieves these aims by inactivating mitogen-activated protein kinase (MAPK) and nuclear factor kappaB signaling pathways. YopJ was shown to bind to members o...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/cb600261k
更新日期:2006-07-21 00:00:00
abstract::Modern visualization techniques are affording a peek into complex cellular processes. A recent paper describes an automated fluorescence microscopy method to map the subcellular localization of up to 100 different proteins in the same sample. ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb600461v
更新日期:2006-12-15 00:00:00
abstract::Small molecules that bind to voltage-gated sodium channels (VGSCs) are promising leads in the treatment of numerous neurodegenerative diseases and pain. Nature is a highly skilled medicinal chemist in this regard, designing potent VGSC ligands capable of binding to and blocking the channel, thereby offering compounds ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00123
更新日期:2019-05-17 00:00:00
abstract::Creation of an artificial oscillating gene expression system is one of the most challenging issues in synthetic biology. Here, we constructed a simple system to manipulate gene expression patterns to be circadian, reflecting the intrinsic cellular clock, by fusing a core clock protein, BMAL1 or CLOCK, with a zinc fing...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb300432s
更新日期:2012-11-16 00:00:00
abstract::Generating highly selective probes to interrogate protein kinase function in biological studies remains a challenge, and new strategies are required. Herein, we describe the development of the first highly selective and cell-permeable inhibitor of c-Src, a key signaling kinase in cancer. Our strategy involves extensio...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb300172e
更新日期:2012-08-17 00:00:00
abstract::Elevation of reactive oxygen species (ROS) levels has been observed in many cancer cells relative to nontransformed cells, and recent reports have suggested that small-molecule enhancers of ROS may selectively kill cancer cells in various in vitro and in vivo models. We used a high-throughput screening approach to ide...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb300653v
更新日期:2013-05-17 00:00:00
abstract::The display and analysis of proteins expressed on biological surfaces has become an attractive tool for the study of molecular interactions in enzymology, protein engineering, and high-throughput screening. Among the growing number of established display systems, retroviruses offer a unique and fully mammalian platfor...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/cb100285n
更新日期:2011-01-21 00:00:00
abstract::Clostridium difficile, a leading cause of hospital-acquired infection, possesses a dense surface layer (S-layer) that mediates host-pathogen interactions. The key structural components of the S-layer result from proteolytic cleavage of a precursor protein, SlpA, into high- and low-molecular-weight components. Here we ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb9002859
更新日期:2010-03-19 00:00:00
abstract::A major risk for patients having estrogen receptor α (ERα)-positive breast cancer is the recurrence of drug-resistant metastases after initial successful treatment with endocrine therapies. Recent studies have implicated a number of activating mutations in the ligand-binding domain of ERα that stabilize the agonist co...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.8b00877
更新日期:2018-12-21 00:00:00
abstract::We evaluated the abilities of an antisense oligonucleotide (ASO), a small interfering RNA (siRNA), and a single-stranded siRNA (ss-siRNA) to inhibit expression from the PTEN gene in mice when formulated identically with lipid nanoparticles (LNPs). Significantly greater reductions in levels of PTEN mRNA were observed f...
journal_title:ACS chemical biology
pub_type: 信件
doi:10.1021/cb4001316
更新日期:2013-07-19 00:00:00
abstract::The 3D structure of a protein is determined by the unique sequence of amino acid residues comprising the polypeptide chain. Sequence changes can cause protein misfolding, a potentially toxic phenomenon implicated in various neurodegenerative disorders. In a recent paper, translational misincorporation is proposed to b...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/cb6004068
更新日期:2006-10-24 00:00:00